title: Protein kinase C gamma interneurons in the rat medullary dorsal horn: distribution and synaptic inputs to these neurons, and subcellular localization of the enzyme.
abstract: The γ isoform of protein kinase C (PKCγ), which is concentrated in interneurons in the inner part of lamina II (IIi ) of the dorsal horn, has been implicated in the expression of tactile allodynia. Lamina IIi PKCγ interneurons were shown to be activated by tactile inputs and to participate in local circuits through which these inputs can reach lamina I, nociceptive output neurons. That such local circuits are gated by glycinergic inhibition and that A- and C-fibers low threshold mechanoreceptors (LTMRs) terminate in lamina IIi raise the general issue of synaptic inputs to lamina IIi PKCγ interneurons. Combining light and electron microscopic immunochemistry in the rat spinal trigeminal nucleus, we show that PKCγ-immunoreactivity is mostly restricted to interneurons in lamina IIi of the medullary dorsal horn, where they constitute 1/3 of total neurons. The majority of synapses on PKCγ-immunoreactive interneurons are asymmetric (likely excitatory). PKCγ-immunoreactive interneurons appear to receive exclusively myelinated primary afferents in type II synaptic glomeruli. Neither large dense core vesicle terminals nor type I synaptic glomeruli, assumed to be the endings of unmyelinated nociceptive terminals, were found on these interneurons. Moreover, there is no vesicular glutamate transporter 3-immunoreactive bouton, specific to C-LTMRs, on PKCγ-immunoreactive interneurons. PKCγ-immunoreactive interneurons contain GABAA ergic and glycinergic receptors. At the subcellular level, PKCγ-immunoreactivity is mostly concentrated on plasma membranes, close to, but not within, postsynaptic densities. That only myelinated primary afferents were found to contact PKCγ-immunoreactive interneurons suggests that myelinated, but not unmyelinated, LTMRs play a critical role in the expression of mechanical allodynia.
authors.affiliation: Inserm/UdA U1107, Neuro-Dol: Trigeminal Pain and Migraine, Université d'Auvergne, Faculté de Chirurgie Dentaire, Clermont-Ferrand, 63000, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Peirs
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Patil
authors.forename: Rabia
authors.initials: R
authors.lastname: Bouali-Benazzouz
authors.forename: Alain
authors.initials: A
authors.lastname: Artola
authors.forename: Marc
authors.initials: M
authors.lastname: Landry
authors.forename: Radhouane
authors.initials: R
authors.lastname: Dallel
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006930:Hyperalgesia / Q000378:metabolism*; D007150:Immunohistochemistry; D007395:Interneurons / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008465:Mechanoreceptors / Q000201:enzymology* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D009619:Nociceptors / Q000201:enzymology / Q000648:ultrastructure; D020671:Posterior Horn Cells / Q000201:enzymology / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000201:enzymology / Q000648:ultrastructure*
chemical_list: C087857:protein kinase C gamma; D011493:Protein Kinase C
keywords: C-low threshold mechanoreceptor (C-LTMR); confocal microscopy; electron microscopy; glycine receptor; medullary dorsal horn (MDH); protein kinase C gamma (PKCγ); vesicular glutamate transporter 3 (VGLUT3); γ-aminobutyric acid type A receptor (GABAA)